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利用抗人mdr1单克隆抗体检测捻转血矛线虫中P-糖蛋白介导的抗驱虫药多药耐药性

Detection of P-glycoprotein-mediated multidrug resistance against anthelmintics in Haemonchus contortus using anti-human mdr1 monoclonal antibodies.

作者信息

Kerboeuf D, Guégnard F, Vern Y Le

机构信息

UR-086, MultiResistances and Antiparasitic drugs, INRA, 37380 Nouzilly, France.

出版信息

Parasitol Res. 2003 Sep;91(1):79-85. doi: 10.1007/s00436-003-0942-2. Epub 2003 Jul 29.

DOI:10.1007/s00436-003-0942-2
PMID:12898231
Abstract

The "multidrug resistance" (MDR) system involves the action of transmembrane P-glycoproteins (Pgp) which may be responsible for failure of chemotherapy in both invertebrates and vertebrates. We previously obtained partial reversion of anthelmintic resistance in nematodes subjected to both anthelmintics and inhibitors of this system. The results presented here are able to describe more accurately the presence of Pgp in nematodes because of the use of C219 and UIC2 monoclonal antibodies, which are used for the detection of human and mouse mdr1 gene products. These antibodies demonstrated the presence of Pgp in eggshells. Their role in these structures, which are considered to be passive barriers, remains to be determined. Flow cytometry analyses of the UIC2 staining allowed determination of the resistance of individuals, which varied within the parasite population. UIC2 demonstrated both the presence and activity of Pgp in nematodes as has previously been shown in tumour cells. Resistance seems to be due to an increase in both the number of Pgp sites and parasites with high levels of Pgp.

摘要

“多药耐药”(MDR)系统涉及跨膜P-糖蛋白(Pgp)的作用,这可能是导致无脊椎动物和脊椎动物化疗失败的原因。我们之前发现,对线虫同时使用驱虫药和该系统的抑制剂,可使驱虫抗性部分逆转。由于使用了C219和UIC2单克隆抗体(用于检测人类和小鼠mdr1基因产物),此处呈现的结果能够更准确地描述线虫中Pgp的存在情况。这些抗体证实了Pgp存在于卵壳中。它们在这些被视为被动屏障的结构中的作用仍有待确定。对UIC2染色进行的流式细胞术分析能够确定个体的抗性,抗性在寄生虫群体中存在差异。UIC2证实了线虫中Pgp的存在及活性,这与之前在肿瘤细胞中的情况一致。抗性似乎是由于Pgp位点数量增加以及Pgp水平高的寄生虫数量增多所致。

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本文引用的文献

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The ABC transporter genes of Plasmodium falciparum and drug resistance.恶性疟原虫的ABC转运蛋白基因与耐药性
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秀丽隐杆线虫中P-糖蛋白12在伊维菌素表型抗性转化中的主导作用
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Macrocyclic lactones differ in interaction with recombinant P-glycoprotein 9 of the parasitic nematode Cylicocylus elongatus and ketoconazole in a yeast growth assay.在酵母生长试验中,大环内酯类药物与寄生线虫长环圆线虫的重组P-糖蛋白9以及酮康唑的相互作用存在差异。
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Impact of gastrointestinal parasitic nematodes of sheep, and the role of advanced molecular tools for exploring epidemiology and drug resistance - an Australian perspective.绵羊胃肠道寄生线虫的影响,以及探索流行病学和耐药性的先进分子工具的作用——澳大利亚的视角。
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Genetic variants and increased expression of Parascaris equorum P-glycoprotein-11 in populations with decreased ivermectin susceptibility.具有伊维菌素低敏感性的种群中,副蛔虫 P-糖蛋白-11 的遗传变异和表达增加。
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